cAMP-dependent protein kinase isozymes (Type I and Type II) were isolated from the soluble fractions of cardiac tissue from 10-month-old spontaneously hypertensive rats (SHR) which had been maintained for nine months on one of four experimental diets: low protein (LP) (19% protein), standard (STD) (24% protein), high protein (HP) (32% protein) or high methionine (1.9% methionine) (MET) by DEAE-cellulose chromatography. The activity and/or levels of these isozymes were determined to examine the influence of diet on the enzyme's effect on the phosphorylation of cardiac regulatory proteins. In the presence of cAMP the activity of the Type I protein kinase was reduced by 3 and 4-fold in the LP diet group compared to the SHR on 32% and methionine diet groups respectively. Type II protein kinase from all four diet groups exhibited similar activities in the presence and absence of cAMP. While cAMP-binding activities in the cardiac fractions from STD, HP and MET groups of rats correlate to protein kinase activities, cAMP-binding activities in the cardiac fractions from the LP group of rats by contrast were higher than enzyme activities. In the phospholamban (sarcoplasmic reticulum (SR) protein whose phosphorylation regulates CA2+ transport mediated by [Ca2+-Mg2+]-ATPase) phosphorylation study, addition of cAMP significantly stimulated phospholamban phosphorylation in all diet groups but the extent of stimulation was highest in the MET group of animals and lowest in the LP groups was not significant. The decrease in the activity of Type I isozyme found in the cardiac fractions from SHR fed low protein diet may be due to a defect in response of the enzyme to cAMP or a reduction in the number of enzyme molecules. Such a condition may affect the degree of phosphorylation of cardiac regulatory proteins, thus impairing cardiac physiology in hypertension.